Transition-metal-free Suzuki-type coupling reactions: scope and limitations of the methodology

The scope and limitations of the transition-metal-free Suzuki-type coupling of aryl halides and arylboronic acids to form biaryls are presented. Confirmation that the reaction is indeed metal-free is presented. The effects of changing base, solvent, reaction temperature, phase-transfer catalyst, and substrate are shown and the implications of these results discussed in terms of their impact on the synthetic versatility of the methodology. The main findings are that the reaction works well for aryl bromides, water is necessary as a solvent for the reaction, the optimum temperature for the reaction is 150 degrees C, the reaction is best performed by using microwave promotion with the exception of an electron-poor aryl bromide example where conventional heating may be used, only limited boronic acids can be used as coupling partners, sodium carbonate is the best base for the reaction, tetrabutylammonium bromide proves to be the best phase-transfer catalyst for the reaction, the reaction is limited to couplings between aryl halides and aryl boronic acids with sp(2)-sp(3) couplings proving ineffective, and NaBPh(4) can be used in the place of phenylboronic acid as a phenylating agent.